PT  - JOURNAL ARTICLE
AU  - Pritykin, Yuri
AU  - van der Veeken, Joris
AU  - Pine, Allison
AU  - Zhong, Yi
AU  - Sahin, Merve
AU  - Mazutis, Linas
AU  - Pe’er, Dana
AU  - Rudensky, Alexander
AU  - Leslie, Christina
TI  - A unified atlas of CD8 T cell dysfunctional states in cancer and infection
AID  - 10.1101/2020.07.25.220673
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.25.220673
4099  - http://biorxiv.org/content/early/2020/07/26/2020.07.25.220673.short
4100  - http://biorxiv.org/content/early/2020/07/26/2020.07.25.220673.full
AB  - CD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across different experimental and clinical settings. By carrying out a unified analysis of over 300 ATAC-seq and RNA-seq experiments from twelve independent studies of CD8 T cell dysfunction in cancer and infection we defined a shared differentiation trajectory towards terminal dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell activation states across models. Experimental dissection of acute and chronic viral infection using scATAC-seq and allele-specific scRNA-seq identified state-specific transcription factors and captured the early emergence of highly similar TCF1+ progenitor-like populations at an early branch point, at which epigenetic features of functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts.Competing Interest StatementThe authors have declared no competing interest.